Possible involvement of DNA breaks in epigenetic regulation of cell differentiation

The review summarizes the authors’ and literature data on accumulation of DNA breaks in differentiating cells. Large 50-kb free DNA fragments were observed by several research teams in non-apoptotic insect, mammal, and plant cells. More intense DNA breakage was observed during maturation of spermatides, embryo development, and differentiation of myotubes, epidermal cells, lymphocytes, and neutrophils. In general, accumulation of DNA breaks in differentiating cells cannot be attributed to a decrease in the DNA repair efficiency. Poly(ADP)ribose synthesis often follows the DNA breakage in differentiating cells. We hypothesize that DNA fragmentation is an epigenetic tool for regulating the differentiation process. Scarce data on localization of the differentiation-associated DNA breaks indicate their preferable accumulation in specific DNA sequences including the nuclear matrix attachment sites. The same sites are degraded at early stages of apoptosis. Recent data on non-apoptotic function of caspases provide more evidence for possible existence of a DNA breakage mechanism in differentiating cells, resembling the initial stage of apoptosis. Excision of methylated cytosine and recombination are other possible explanations of the phenomenon. Elucidation of mechanisms of differentiation-induced DNA breaks appears to be a prospective research direction.     

Diversity,Community Composition,and Dynamics of Nonpigmented and Late-Pigmenting Rapidly Growing Mycobacteria in an Urban Tap Water Production and Distribution System

Nonpigmented and late-pigmenting rapidly growing mycobacteria (RGM) have been reported to commonly colonize water production and distribution systems. However, there is little information about the nature and distribution of RGM species within the different parts of such complex networks or about their clustering into specific RGM species communities. We conducted a large-scale survey between 2007 and 2009 in the Parisian urban tap water production and distribution system. We analyzed 1,418 water samples from 36 sites, covering all production units, water storage tanks, and distribution units; RGM isolates were identified by using rpoB gene sequencing. We detected 18 RGM species and putative new species, with most isolates being Mycobacterium chelonae and Mycobacterium llatzerense. Using hierarchical clustering and principal-component analysis, we found that RGM were organized into various communities correlating with water origin (groundwater or surface water) and location within the distribution network. Water treatment plants were more specifically associated with species of the Mycobacterium septicum group. On average, M. chelonae dominated network sites fed by surface water, and M. llatzerense dominated those fed by groundwater. Overall, the M. chelonae prevalence index increased along the distribution network and was associated with a correlative decrease in the prevalence index of M. llatzerense, suggesting competitive or niche exclusion between these two dominant species. Our data describe the great diversity and complexity of RGM species living in the interconnected environments that constitute the water production and distribution system of a large city and highlight the prevalence index of the potentially pathogenic species M. chelonae in the distribution network.